石菖蒲挥发油活性成分甲基丁香酚靶向JAK2/STAT3通路缓解脑微血管内皮细胞炎症和焦亡OA

OBJECTIVE To investigate the protective effects and potential mechanisms of Acorus tatarinowii volatile oil and its main components(α-asarone,β-asarone,and methyl eugenol)on inflammation and pyroptosis in lipopolysaccharide(LPS)-induced brain microvascular endothelial cells(bEnd.3).METHODS An in vitro inflammation model was established using LPS-stimulated bEnd.3 cells.The LPS-stimulated bEnd.3 cells were then treated with Acorus tatarinowii volatile oil and its main active components(α-asarone,β-asarone,and methyl eugenol)to investigate their effects on inflammation and pyroptosis.Network pharmacology and mo-lecular docking analysis were used to identify potential targets of methyl eugenol.The STAT3 inhibitor Stattic was used to further vali-date the role of the signaling pathway.RESULTS The volatile oil of Acorus tatarinowii and its main active ingredient,methyl euge-nol,both exhibited significant anti-inflammatory and anti-pyroptosis effects,effectively inhibiting inflammation and pyroptosis.Net-work pharmacology analysis suggested that the JAK2/STAT3 signaling pathway might be a potential target of methyl eugenol,and mo-lecular docking experiments further confirmed that methyl eugenol had a strong binding affinity for both JAK2 and STAT3 proteins.In the LPS-induced bEnd.3 cell model,both Acorus tatarinowii volatile oil and methyl eugenol significantly reduced the phosphorylation level of STAT3;simultaneously,the STAT3-specific inhibitor Stattic also inhibited the expression of the pyroptosis marker protein cleaved caspase-1,further validating the key role of this pathway in regulating pyroptosis.CONCLUSION Methyl eugenol can sig-nificantly inhibit LPS-induced pyroptosis and inflammatory responses in bEnd.3 cells by targeting the JAK2/STAT3 signaling path-way.The findings offer a new strategy for the prevention and treatment of neuroinflammation-related diseases.